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Updated: Sep 21, 2025

Assays for Validating Histone Acetyltransferase Inhibitors
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Published on: August 6, 2020

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High Histone Deacetylase 2/3 Expression in Non-Functioning Pituitary Tumors

Wenxiu Zhao1, Xiaobin Jiang1, Karrin Weisenthal1

  • 1Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

Frontiers in Oncology
|June 1, 2022
PubMed

Insights

Histone deacetylase (HDAC) inhibition and DNA methylation targeting show promise for treating non-functioning pituitary adenomas. These epigenetic therapies can restore tumor suppressor gene expression, offering a potential new treatment strategy.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cancer Research

Background:

  • Epigenetic modifications, including chromatin changes, are implicated in pituitary neoplasia.
  • These alterations affect tumor suppressor and oncogene expression and may be reversible.
  • The specific role of histone deacetylases (HDACs) in pituitary tumorigenesis remains unclear.

Purpose of the Study:

  • To investigate the expression of Class I HDACs in non-functioning pituitary adenomas (NFPAs).
  • To evaluate the therapeutic potential of targeting HDACs and DNA methylation in NFPAs.

Main Methods:

  • RT-PCR and immunohistochemical staining (IHC) to assess HDAC2 and HDAC3 expression in NFPAs versus normal pituitary (NP) samples.
  • In vitro treatment of a human NFPA cell line (PDFS) with an HDAC3 inhibitor (RGFP966) and a DNA methyltransferase (DNMT) inhibitor (5'-aza-2'-deoxycytidine).
  • Assessment of cell proliferation and tumor suppressor gene expression (STAT1, P16, PTEN, MEG3).

Main Results:

  • HDAC2 and HDAC3 were significantly upregulated in NFPAs compared to NP samples.
  • HDAC3 inhibition with RGFP966 reduced PDFS cell proliferation by 70%.
  • Combined inhibition of HDAC3 and DNMT restored expression of tumor suppressor genes STAT1, P16, PTEN, and MEG3.

Conclusions:

  • Both histone modification and DNA methylation are involved in the pathogenesis of human NFPAs.
  • Targeting HDACs and DNA methylation represents a promising therapeutic strategy for NFPAs.
Keywords:
class I histone deacetylasesepigenetic modificationsgrowth suppressionhuman clinically non-functioning pituitary adenomasregulation of tumor suppressor expressions

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